PepTalk 2017
PepTalk 2017
2014 Archived Content

Cambridge Healthtech Institute’s Second Annual
Extractables and Leachables
Addressing Toxicological and Biochemical Challenges for Drug Product Integrity
January 16-17, 2014


Day 1 | Day 2 | Download Development Brochure | Speaker Biographies 


7:15 am Conference Registration

7:30 Breakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee


8:30 Chairperson’s Remarks

Pranhitha Reddy, Director, Cell Sciences, BioProcess and Analytical Sciences, Seattle Genetics

8:35 Leachable and Extractable Study Design for Components Used Across Multiple Programs

Seamus O'ConnorSeamus O’Connor, Ph.D., Senior Analytical Scientist, Analytical Sciences, Industrial Operations and Product Supply, Regeneron Pharmaceuticals, Inc.

In multi-product facilities frequently common components are used for multiple products, many of which have similar or identical formulations. An extractable/leachable strategy has been developed to leverage information between programs to conduct the studies in a more efficient manner.

9:05 Risk-Based Assessment of Extractable Data and Its Application to the Evaluation of Materials Used in the Biomanufacturing

Ping WangPing Wang, Ph.D., MBA, Senior Manager, Pharmaceutical & Material Sciences, DPD, PDMS, Janssen Research & Development

Though the application of polymeric disposable materials in the biomanufacturing process has become more popular, the extractables and leachables (E&L) are the major concerns from safety and quality perspective. The lack of relevant E&L data from suppliers presents end-users a great challenge. Strategies of developing relevant extractable data and applying that in the evaluation of safety concern threshold level will be discussed.

9:35 Leachables from Unexpected Sources

Michael RubertoMichael A. Ruberto, Ph.D., President, Material Needs Consulting, LLC

There have been many reports in the literature about leachables entering drugs from unexpected sources such as secondary packaging, labels, bulk shipping containers, and pallets. This presentation will discuss these issues as well as provide some concrete measures that can be taken to reduce their risk, and allow pharmaceutical companies to have more control over their supply chain and be better equipped handle these incidents when they do occur.

10:05 Selected Oral Poster Presentation: Feasibility of Using Disposable Mixing Systems for Homogenizing Biologic Drug Substance Bulk

Benson Gikanga, Sr. Research Associate, Pharmaceutical Processing and Technology Development, Genentech, Inc.

Protein shear resulting from magnetic coupling of bottom mounted impeller and drive unit via female and male bearing is often observed during drug substance homogenization. Disposable mixing systems incorporating newer and advanced technologies can address this challenge. Mixers evaluated in this study using a monoclonal antibody indicate that levitating impeller technology can offer a better mixing option in terms of particle generation, impact on product quality, and filter fouling during filtration.

10:20 Coffee Break in the Exhibit Hall with Poster Awards

11:15 Analytical Testing For Low Level Leachables in Large Volume Parenteral Products: Analytical Method Development and Validation Issues for Trace Level Testing

Gyorgy VasGyorgy Vas, Ph.D., Research Fellow, Intertek Pharmaceutical Services

Injectable dosage forms are often stored in a polymer based bags or containers, therefore represent one of the highest risk drug products in relation to the potential introduction of impurities via container closure contact, since any leachable can be rapidly and completely introduced into the patient’s general circulation. The daily doses of those products are often one liter or above, therefore the analytical testing at the SCT level of 0.15 μg/day can be a challenging analytical task. Analytical methods and validation aspects will be presented to analyze the organic and inorganic leachable components at sub-parts-per-billion level.

Case Studies: Impact of E&L From Single-Use Technologies 

Featured Presentation


11:45 Extractables from Single-Use Bioreactors and Impact on Cell Culture Performance

Yasser Nashed-SamuelYasser Nashed-Samuel, Ph.D., Principal Scientist, Process and Product Development, Amgen, Inc.

Biopharmaceuticals are drugs manufactured by growing genetically engineered cells in bioreactors to produce a therapeutic protein. Plastic single use bioreactors are of interest to biopharmaceutical drug manufacturers due its significant environmental and cost benefits and flexibility over stainless steel bioreactors. Effect of plastics on the biomanufacturing process is not yet completely understood. A case study on extractables from single use bioreactors and impact on cell culture performance will be presented.

12:15 pm Case Studies on the Impact of Disposables on Cell Culture Processes

Pranhitha Reddy, Director, Cell Sciences, BioProcess and Analytical Sciences, Seattle Genetics

The availability of single use and disposable technologies for cell culture processes has enabled the establishment and prevalence of “flexible manufacturing” in upstream areas. This presentation provides case studies on the successful implementation of single use technologies in our platform, and illustrates our investigations and responses to the negative impact of E&L from disposables encountered in upstream processing. Potential constraints in “flexible manufacturing” and risk mitigation strategies that are applicable to cell culture platforms that use disposables in manufacturing will be discussed.

12:45 Sponsored Presentation (Opportunity Available)

1:15 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own

Ensuring SafEty and Efficacy of Biologics 

2:00 Chairperson’s Remarks

Christian SchoeneichChristian Schöneich, Ph.D., Professor and Chair, Pharmaceutical Chemistry, University of Kansas


2:05 Structure-based Predictive Modeling of Methionine Oxidation Stability in Proteins

Vishal Nashine

Vishal C. Nashine, Ph.D., Senior Research Investigator, Drug Product Science & Technology, Bristol-Myers Squibb Co.

Oxidation of Methionine (Met) residues in therapeutic proteins may significantly impact their safety and efficacy. Met oxidation may also result in protein aggregation. We describe application of MD simulations towards prediction of the oxidation propensities of Met within several proteins.  Our results show that the 2-shell water coordination number (2-SWCN) and simulation averaged solvent accessible area (SAA) are highly predictive of the relative oxidation rates of Met residues.

2:35 Correlating Monoclonal Antibody Stability with Local Dynamics using H/D Exchange Mass Spectrometry

Prakash ManikwarPrakash Manikwar, Ph.D., Scientist I, Formulation Sciences, MedImmune, Inc.

In this study, we investigated how sucrose and arginine impact both thelocal flexibility and physical stability of an IgG1 mAb. These excipients showed differential effects on conformational stability, storage stability, aggregation rates, and local flexibility of the mAb. New insights and preliminary correlations between local flexibility within specific segments of the CH2 domain and the mAb’s overall physical stability will be provided. 

3:05 Overview of Current Glass Delamination Issues and Implications

Ed SmithEdward J. Smith, Ph.D., Principal, Packaging Science Resources, LLC

Recently there have been many reports of significant recalls due to particulate matter in vials of drug products due to glass delamination which is a combination of chemical alteration and mechanical failure of the glass surface. This presentation will discuss the types of drugs and vials that present the most risk and review the efforts of glass manufacturers, drug packagers, and standards organizations to assess risk and preclude recalls.

3:35 Adapting to Biology: Maintaining Container Closure System Compatibility with the Biopharmaceutical Revolution

Dominick DeGrazioDominick DeGrazio, Associate Scientist, Analytical Laboratory, West Pharmaceutical Services

Alternative measures must be established that aim to preserve the efficacy and functionality of a biologic—from production to patient administration. Sustaining a stable equilibrium for proteins depends upon the ability of container closure systems to maintain compatibility with biological dynamics. Failure of packaging components to adapt can compromise patient safety, drug productivity, and biological stability.

4:05 Close of Conference

Day 1 | Day 2 | Download Development Brochure | Speaker Biographies